This invention relates to certain indenofurans and indenothiophenes having diuretic-saluretic and antihypertensive pharmacological activity. Further, this invention relates to processes for the preparation of such compounds; pharmacological compositions comprising such compounds; and to methods of treatment comprising administering such compounds and compositions for the alleviation of symptoms associated with electrolyte imbalance and fluid retention such as hypertension and edema.
The compounds of this invention may be represented by the following generic structure: ##SPC1##
Wherein the dotted lines indicate 1,2-, 7,8-, and 1,2,7,8-unsaturated embodiments; A is oxygen or sulfur; R is hydrogen, lower alkyl or halo; R.sup.1 is lower alkyl, cycloalkyl, or aralkyl; or R and R.sup.1, together with the carbon atom to which they are attached, may be joined to form a cycloalkyl radical having from 3 to about 6 carbon atoms; R.sup.2 is hydrogen, lower alkyl, or phenyl; X.sup.1 is lower alkyl or halo; X.sup.2 is hydrogen, lower alkyl or halo. A 7-alkylidene embodiment is characterized in that the substituent at the 7-position is =CR.sup.3 R.sup.4 ; wherein R.sup.3 and R.sup.4 are independently selected from the group consisting of hydrogen, lower alkyl, cycloalkyl, aryl, and aralkyl.
Also within the scope of the present invention are the respective salt, ester and amide derivatives of the above-described compounds.
For convenience, these compounds will collectively be referred to hereinafter as "indenofurans".
Pharmacological studies show that the indenofurans of the present invention are effective diuretic and saluretic agents which can be used in the treatment of conditions associated with electrolyte and fluid retention such as edema and hypertension. Thus, when administered in therapeutic dosages in conventional vehicles, the compounds of this invention effectively reduce the amount of sodium and chloride ions in the body, lower dangerous excesses of fluid levels to acceptable levels and in general alleviate conditions associated with edema and hypertension.
Thus it is an object of the present invention to provide the indenofurans of the above general description and to provide processes for preparation of such compounds. Further objects of this invention are to provide pharmaceutical compositions comprising such indenofurans and to provide methods of treatment comprising administering such compounds and compositions.